The Eraser in the Brain – Alzheimer’s Disease

【Early Symptoms】

1. Memory loss that affects daily life
2. Decline in the ability to plan and solve problems
3. Difficulty in completing tasks that were once familiar
4. Confusion about time and place
5. Misunderstanding of visual images and spatial relationships
6. Problems with linguisticexpression and writing
7. Misplacing things and losing the ability to retrace steps to find them
8. Decreased judgment
9. Gradual withdrawal from work and social activities
10. Changes in mood and personality

【Key Targets】

Overview of Alzheimer’s Disease related genes

Fig 1. The inner color corresponds to its regulatory function. If there are two inner colors, it means that the gene is involved in more than one pathway. The genes circled in yellow are also believed to affect the metabolism of amyloid precursor protein; the genes circled in red are believed to affect the metabolism of tau protein. ^[1].

【Brief Analysis of Alzheimer’s Disease Mechanism】

In General, amyloid precursor protein (APP) undergoes nonamyloidogenic processing. It is first cleaved by α-secretase to generate sAPPα and C83 carboxyl terminal fragments, and then C83 is cleaved by γ-secretase to P3 and AICD, which participate in subsequent regulation. Under pathological conditions, APP undergoes amyloidogenic processing. It is first cleaved by β-secretase to generate sAPPβ and C99 fragments, and then γ-secretase cleaves C99 and releases Aβ40/42 extracellular fragments. Overproduction of Aβ40/42 and/or failure of Aβ clearance mechanisms lead to Aβ self-aggregation to form oligomers, which not only form plaques but also induce hyperphosphorylation of Tau protein, thereby destabilizing microtubules and ultimately causing neurofibrillary tangles.

In addition, the aggregation of Aβ40/42 can also lead to calcium homeostasis imbalance, endoplasmic reticulum stress, mitochondrial dysfunction, energy metabolism impairment, and glucose regulation abnormality, ultimately causing nerve cell death. ^[1-10]

References：

• Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur J Neurol. 2018 Jan;25(1):59-70.
• Bossy-Wetzel E, Schwarzenbacher R, Lipton SA (2004) Molecular pathways to neurodegeneration. Nat. Med. 10 Suppl, S2–9.
• Chen JX, Yan SS (2010) Role of mitochondrial amyloid-beta in Alzheimer’s disease. J. Alzheimers Dis. 20 Suppl 2, S569–78.
• Claeysen S, Cochet M, Donneger R, Dumuis A, Bockaert J, Giannoni P (2012) Alzheimer culprits: cellular crossroads and interplay. Cell. Signal. 24(9), 1831–40.
• Marcus JN, Schachter J (2011) Targeting post-translational modifications on tau as a therapeutic strategy for Alzheimer’s disease. J. Neurogenet. 25(4), 127–33.
• Müller WE, Eckert A, Kurz C, Eckert GP, Leuner K (2010) Mitochondrial dysfunction: common final pathway in brain aging and Alzheimer’s disease–therapeutic aspects. Mol. Neurobiol. 41(2-3), 159–71.
• Nizzari M, Thellung S, Corsaro A, Villa V, Pagano A, Porcile C, Russo C, Florio T (2012) Neurodegeneration in Alzheimer disease: role of amyloid precursor protein and presenilin 1 intracellular signaling. J Toxicol 2012, 187297.
• Thinakaran G, Koo EH (2008) Amyloid precursor protein trafficking, processing, and function. J. Biol. Chem. 283(44), 29615–9.
• Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020). Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease. Molecular Neurodegeneration 15.
• Lane, C. A., Hardy, J., & Schott, J. M. (2018). Alzheimer’s disease. European Journal of Neurology 25(1), 59–70.

【Star Product】

Alzheimer’s disease small molecule compound Kit-1 （IK-AD-1）https://en.solarbio.com/goodsInfo?id=89189

This kit carefully selects several compounds targeting Amyloid-β, which   can be used in Alzheimer’s disease-related research and facilitate operations

such as preliminary screening for customers. Customers can also flexibly customize exclusive kits according to their own needs.

1. It has good biological activity and is available in small packaging, which can be used for preliminary screening, pre-experiments, preliminary verification andother operations.
2. Targeting receptors such as Amyloid-β.
3. Can be used to explore Alzheimer’s disease-related research, such as molecular mechanisms, pathological activities, etc.
4. Customers can flexibly customize the kit according to their experimental needs: specifications, kit composition, product types, quantity, form (solution/powder) can all be customized.

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【Star Product】

Thioflavin T（IT3780）https://en.solarbio.com/goodsInfo?id=176467

Thioflavin T (ThT) is a cationic benzothiazole dye. When bound to amyloid proteins in tissue sections, its fluorescence intensity increases, and it is commonly used in research related to the diagnosis of amyloid fibrils. When Thioflavin T binds to β-sheets, such as those in amyloid oligomers, the dye undergoes a characteristic 120 nm red shift in its excitation spectrum. It can be selectively excited at 450 nm, generating a fluorescence signal at 482 nm.Thioflavin T rapidly and specifically binds to the antiparallel β-sheet fibrils formed by synthetic amyloid β (1-40), but does not bind to monomers or oligomeric intermediates. The binding of Thioflavin T does not interfere with the aggregation of amyloid β into amyloid fibrils. This dye is often used to visualize plaques composed of amyloid β, which are found in the brains of patients with Alzheimer’s disease.

                                                               Gao LJ, et al. Phytother Res. 2021 Mar,35(3):1572-1584.

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【Star Product】

Thioflavin T（Cat.No IT3780）

Thioflavin T (ThT) is a cationic benzothiazole dye. When bound to amyloid proteins in tissue sections, its fluorescence intensity increases, and it is commonly used in research related to the diagnosis of amyloid fibrils. When Thioflavin T binds to β-sheets, such as those in amyloid oligomers, the dye undergoes a characteristic 120 nm red shift in its excitation spectrum. It can be selectively excited at 450 nm, generating a fluorescence signal at 482 nm.Thioflavin T rapidly and specifically binds to the antiparallel β-sheet fibrils formed by synthetic amyloid β (1-40), but does not bind to monomers or oligomeric intermediates. The binding of Thioflavin T does not interfere with the aggregation of amyloid β into amyloid fibrils. This dye is often used to visualize plaques composed of amyloid β, which are found in the brains of patients with Alzheimer’s disease.

Gao LJ, et al. Phytother Res. 2021 Mar;35(3):1572-1584.

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